CELSR2-PSRC1-SORT1 gene expression and association with coronary artery disease and plasma lipid levels in an Asian Indian cohort
CELSR2-PSRC1-SORT1 gene expression and association with coronary artery disease and plasma lipid levels in an Asian Indian cohort
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DOI：
10.1016/j.jjcc.2014.02.012
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发表时间：
2014-11-01
影响因子：
2.5
通讯作者：
Shanker, Jayashree
中科院分区：
文献类型：
--
作者：
Arvind, Prathima;Nair, Jiny;Shanker, Jayashree
背景：血脂的遗传调节已被证明影响冠状动脉疾病（CAD）的风险。我们分析了在CELSR 2-PSRC 1-SORT 1基因簇中存在的rs 599839和rs646776单核苷酸多态性（SNP）之间的关系、候选基因表达以及它们与CAD和循环脂质水平的关联，这些关联来自印度动脉粥样硬化研究中的亚洲印度人的代表性队列。采用Taqman分析法对1034例CAD患者和1034例年龄和性别匹配的对照者进行SNPs rs 599839和rs646776基因分型。在100例病例和100例对照中检测CELSR 2、PSRC 1和SORT 1基因的表达。采用酶法测定血浆总胆固醇（TC）、甘油三酯、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）水平。rs646776和rs 599839均处于强连锁不平衡状态（r = 0.98），并显示出与CAD显著的保护性相关性（OR= 0.315，95%CI 0.136-0.728，p < 0.007和OR = 0.422，95%CI 0.181-0.981，p = 0.045）。单倍型TA的频率为72%，与CAD相关（OR 0.77.95%CI 0.67-0.88，p = 0.0002）。PSRC 1基因表达在病例组低于对照组（0.75 +/- 0.405 vs 1.04 +/- 0.622，p = 2.26 x 10（-4））。纯合变异和杂合基因型显示PSRC 1表达分别高出30%和15%。相应地，次要等位基因与较低的血浆TC和LDL-c level.Conclusion：PSRC 1的胆固醇基因簇中显示了显着的关联凭借的两个SNPs，rs646776和rs 599839，也调节血浆胆固醇水平与CAD。(C)2014年日本心脏病学院。由爱思唯尔有限公司出版。保留所有权利。
Background: Genetic regulation of plasma lipids has been shown to influence the risk of coronary artery disease (CAD). We analyzed the relationship between rs599839 and rs646776 single nucleotide polymorphisms (SNPs) present in the CELSR2-PSRC1-SORT1 gene cluster, candidate gene expression, and their association with CAD and circulating lipid levels in a representative cohort of Asian Indians selected from the Indian Atherosclerosis Research Study.Methods: SNPs rs599839 and rs646776 were genotyped by Taqman assay in 1034 CAD patients (cases) and 1034 age- and gender-matched controls. Expression of CELSR2, PSRC1, and SORT1 genes was measured in 100 cases and 100 controls. Plasma levels of total cholesterol (TC), triglycerides, high-density lipoproteincholesterol, and low-density lipoprotein-cholesterol (LDL-c) were measured by enzymatic assay.Results: Both rs646776 and rs599839 were in strong linkage disequilibrium (r = 0.98) and showed significant protective association with CAD (OR= 0.315, 95% CI 0.136-0.728, p < 0.007 and OR = 0.422, 95% CI 0.181-0.981, p = 0.045, respectively). Haplotype TA showed 72% frequency and was associated with CAD (OR 0.77.95% CI 0.67-0.88, p = 0.0002). PSRC1 gene expression was lower in the cases than in the controls (0.75 +/- 0.405 versus 1.04 +/- 0.622, p = 2.26 x 10(-4)). The homozygous variant and heterozygous genotypes showed 30% and 15% higher PSRC1 expression, respectively. Correspondingly, the minor alleles were associated with lower plasma TC and LDL-c levels.Conclusion: PSRC1 in the cholesterol gene cluster shows a significant association with CAD by virtue of the two SNPs, rs646776 and rs599839 that also regulate plasma cholesterol levels. (C) 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.